EFHD1 promotes breast cancer progression through estrogen signaling

Abstract

Background: EF-hand domain family member D1 (EFHD1) is a novel mitochondrial regulator. EFHD1 has been reported in the progression of many types of cancer, such as osteosarcoma, clear cell renal cell carcinoma, and colorectal cancer. Our study aimed to investigate the mechanisms of EFHD1 in breast cancer (BRCA).

Methods: EFHD1 expression was detected in samples of patients with BRCA using quantitative real-time PCR, Western blot, and immunohistochemistry. Cell proliferation was determined using EdU assay. Cell apoptosis was examined using flow cytometry. Meanwhile, cell migration and cell invasion were detected using wound healing assay and Transwell assay. The expression levels of protein involved in ERα signaling were determined using quantitative real-time PCR and Western blot.

Results: EFHD1 expression was elevated in samples of patients with BRCA, which is associated with poor outcome. EFHD1 knockdown inhibited BRCA cell proliferation, migration, and invasion. EFHD1 overexpression promoted BRCA cell proliferation, migration, and invasion. Through gene set enrichment analysis, it was discovered that EFHD1 activated estrogen signaling. ESR1 knockdown treatment abolished the effects of EFHD1 overexpression on cell proliferation, apoptosis, and migration.

Conclusions: Our findings suggested that EFHD1 promoted BRCA progression through enhancing estrogen signaling. EFHD1/ESR1 may serve as a potential therapeutic target for treating BRCA.

Keywords: Breast cancer; EFHD1; Estrogen signaling.